ETS-1 oncogenic activity mediated by transforming growth factor α

Chet E. Holterman, Aleksandra Franovic, Josianne Payette, Stephen Lee

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Inappropriate expression of Ets-1 is observed in a variety of human cancers, and its forced expression in cultured cells results in transformation, autonomous proliferation, and tumor formation. The basis by which Ets-1 confers autonomous growth, one of the primary hallmarks of cancer cells and a critical component of persistent proliferation, has yet to be fully explained. Using a variety of cancer cell lines, we show that inhibition of Ets-1 blocks tumor formation and cell proliferation in vivo and autonomous growth in culture. A screen of multiple diffusible growth factors revealed that inhibition of Ets-1 results in the specific down-regulation of transforming growth factor α (TGFα), the proximal promoter region of which contains multiple ETS family DNA binding sites that can be directly bound and regulated by Ets-1. Notably, rescuing TGFα expression in Ets-1-silenced cells was sufficient to restore tumor cell proliferation in vivo and autonomous growth in culture. These results reveal a previously unrecognized mechanism by which Ets-1 oncogenic activity can be explained in human cancer through its ability to regulate the important cellular mitogen TGFα.

Original languageEnglish (US)
Pages (from-to)730-740
Number of pages11
JournalCancer Research
Volume70
Issue number2
DOIs
StatePublished - Jan 15 2010
Externally publishedYes

Fingerprint

Transforming Growth Factors
Neoplasms
Growth
Cell Proliferation
Mitogens
Genetic Promoter Regions
Cultured Cells
Intercellular Signaling Peptides and Proteins
Down-Regulation
Binding Sites
Cell Line
DNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

ETS-1 oncogenic activity mediated by transforming growth factor α. / Holterman, Chet E.; Franovic, Aleksandra; Payette, Josianne; Lee, Stephen.

In: Cancer Research, Vol. 70, No. 2, 15.01.2010, p. 730-740.

Research output: Contribution to journalArticle

Holterman, Chet E. ; Franovic, Aleksandra ; Payette, Josianne ; Lee, Stephen. / ETS-1 oncogenic activity mediated by transforming growth factor α. In: Cancer Research. 2010 ; Vol. 70, No. 2. pp. 730-740.
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